Platelet Inhibitory Effect of Clopidogrel in Patients Treated With Omeprazole, Pantoprazole, or Famotidine

This study has been completed.
Sponsor:
Collaborator:
Tel Aviv Medical Center
Information provided by (Responsible Party):
michal roll, Tel-Aviv Sourasky Medical Center
ClinicalTrials.gov Identifier:
NCT00950339
First received: April 19, 2009
Last updated: July 6, 2016
Last verified: July 2016
  Purpose

Current guidelines recommend the addition of proton pump inhibitors (PPI) to patients taking double anti-platelet therapy (Aspirin and Clopidogrel) to prevent upper GI bleeding1. Many post percutaneous coronary intervention (PCI) patients are treated with dual anti-platelet medications as well as PPI to prevent upper GI bleeding.

Recently, it was shown that PPI interact with the P450 system in the liver and reduce the platelet inhibitory effect of Clopidogrel2,3. Clopidogrel is activated by CYP2C19, which also metabolizes PPI4. Furthermore, a recent article showed increased mortality in patients taking PPI and clopidogrel compared with patients taking clopidogrel without PPI protection5. The degree of reduction in the platelet inhibitory properties of clopidogrel might vary among the different PPI4.

The use of PPI for GI protection in patients treated with dual anti-platelet therapy is not based on randomized trials, but rather on expert opinion. Since H2 blockers are also effective in preventing acid secretion and are not known to interact with the P450 system that affects clopidogrel, the investigators hypothesized that these group of drugs will not interfere with the positive antiplatelet effects of clopidogrel and therefore will offer a good alternative treatment option.


Condition Intervention Phase
Coronary Heart Disease
GI Bleeding
Drug: omeprazole, 20mg twice daily
Drug: famotidine 40mg twice daily
Drug: pantoprazole 40mg once daily
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Platelet Inhibitory Effect of Clopidogrel in Patients Treated With Omeprazole, Pantoprazole, or Famotidine

Resource links provided by NLM:


Further study details as provided by Tel-Aviv Sourasky Medical Center:

Primary Outcome Measures:
  • Platelet function as assessed by a CPA system [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Enrollment: 63
Study Start Date: August 2009
Study Completion Date: August 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 4 weeks of omeprazole, 20mg twice daily

Each patient will undergo 3 phases of drug therapy:

A- 4 weeks of PPI treatment (omeprazole, 20mg twice daily)) B- 4 weeks of H2 blocker treatment (famotidine 40mg twice daily) C- 4 weeks of PPI treatment (pantoprazole 40mg once daily).

At the end of each phase- each patient will undergo the following evaluation:

Platelet reactivity

Drug: omeprazole, 20mg twice daily

Each patient will undergo 3 phases of drug therapy:

A- 4 weeks of PPI treatment (omeprazole, 20mg twice daily)) B- 4 weeks of H2 blocker treatment (famotidine 40mg twice daily) C- 4 weeks of PPI treatment (pantoprazole 40mg once daily).

At the end of each phase- each patient will undergo the following evaluation:

Platelet reactivity

Other Name: PPI Platelet Inhibitory
Drug: famotidine 40mg twice daily

Each patient will undergo 3 phases of drug therapy:

A- 4 weeks of PPI treatment (omeprazole, 20mg twice daily)) B- 4 weeks of H2 blocker treatment (famotidine 40mg twice daily) C- 4 weeks of PPI treatment (pantoprazole 40mg once daily).

At the end of each phase- each patient will undergo the following evaluation:

Platelet reactivity

Other Name: PPI Platelet Inhibitory
Drug: pantoprazole 40mg once daily

Each patient will undergo 3 phases of drug therapy:

A- 4 weeks of PPI treatment (omeprazole, 20mg twice daily)) B- 4 weeks of H2 blocker treatment (famotidine 40mg twice daily) C- 4 weeks of PPI treatment (pantoprazole 40mg once daily).

At the end of each phase- each patient will undergo the following evaluation:

Platelet reactivity

Other Name: PPI Platelet Inhibitory
Experimental: 4 weeks of famotidine 40mg twice daily

Each patient will undergo 3 phases of drug therapy:

A- 4 weeks of PPI treatment (omeprazole, 20mg twice daily)) B- 4 weeks of H2 blocker treatment (famotidine 40mg twice daily) C- 4 weeks of PPI treatment (pantoprazole 40mg once daily).

At the end of each phase- each patient will undergo the following evaluation:

Platelet reactivity

Drug: omeprazole, 20mg twice daily

Each patient will undergo 3 phases of drug therapy:

A- 4 weeks of PPI treatment (omeprazole, 20mg twice daily)) B- 4 weeks of H2 blocker treatment (famotidine 40mg twice daily) C- 4 weeks of PPI treatment (pantoprazole 40mg once daily).

At the end of each phase- each patient will undergo the following evaluation:

Platelet reactivity

Other Name: PPI Platelet Inhibitory
Drug: famotidine 40mg twice daily

Each patient will undergo 3 phases of drug therapy:

A- 4 weeks of PPI treatment (omeprazole, 20mg twice daily)) B- 4 weeks of H2 blocker treatment (famotidine 40mg twice daily) C- 4 weeks of PPI treatment (pantoprazole 40mg once daily).

At the end of each phase- each patient will undergo the following evaluation:

Platelet reactivity

Other Name: PPI Platelet Inhibitory
Drug: pantoprazole 40mg once daily

Each patient will undergo 3 phases of drug therapy:

A- 4 weeks of PPI treatment (omeprazole, 20mg twice daily)) B- 4 weeks of H2 blocker treatment (famotidine 40mg twice daily) C- 4 weeks of PPI treatment (pantoprazole 40mg once daily).

At the end of each phase- each patient will undergo the following evaluation:

Platelet reactivity

Other Name: PPI Platelet Inhibitory
Experimental: 4 weeks of pantoprazole 40mg once daily

Each patient will undergo 3 phases of drug therapy:

A- 4 weeks of PPI treatment (omeprazole, 20mg twice daily)) B- 4 weeks of H2 blocker treatment (famotidine 40mg twice daily) C- 4 weeks of PPI treatment (pantoprazole 40mg once daily).

At the end of each phase- each patient will undergo the following evaluation:

Platelet reactivity

Drug: omeprazole, 20mg twice daily

Each patient will undergo 3 phases of drug therapy:

A- 4 weeks of PPI treatment (omeprazole, 20mg twice daily)) B- 4 weeks of H2 blocker treatment (famotidine 40mg twice daily) C- 4 weeks of PPI treatment (pantoprazole 40mg once daily).

At the end of each phase- each patient will undergo the following evaluation:

Platelet reactivity

Other Name: PPI Platelet Inhibitory
Drug: famotidine 40mg twice daily

Each patient will undergo 3 phases of drug therapy:

A- 4 weeks of PPI treatment (omeprazole, 20mg twice daily)) B- 4 weeks of H2 blocker treatment (famotidine 40mg twice daily) C- 4 weeks of PPI treatment (pantoprazole 40mg once daily).

At the end of each phase- each patient will undergo the following evaluation:

Platelet reactivity

Other Name: PPI Platelet Inhibitory
Drug: pantoprazole 40mg once daily

Each patient will undergo 3 phases of drug therapy:

A- 4 weeks of PPI treatment (omeprazole, 20mg twice daily)) B- 4 weeks of H2 blocker treatment (famotidine 40mg twice daily) C- 4 weeks of PPI treatment (pantoprazole 40mg once daily).

At the end of each phase- each patient will undergo the following evaluation:

Platelet reactivity

Other Name: PPI Platelet Inhibitory

Detailed Description:
In this study we will compare 3 different anti-acids regimens and their effect on platelet function
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject is at least 18 years old.
  2. Subject is willing to comply with pre-specified follow-up evaluation and can be contacted by telephone.
  3. Use of Clopidogrel (>=75mg) and Aspirin(>=75mg) for at least 1 month.

Exclusion Criteria:

  1. Known allergy to PPI of H2 blockers
  2. Known thrombocytopenia or thrombocytopathia
  3. Subject is currently enrolled in another investigational study of a new drug, biologic or device at the time of study screening. NOTE: Subjects who are participating in the long term follow-up phase of a previously investigational and now FDA-approved product are not excluded by this criterion.
  4. Subject with symptomatic heart failure of LVEF ≤ 25%
  5. Acute myocardial infarction within the past 30 days.
  6. No acute inflammatory event during the past month (e.g. infection, autoimmune or acute coronary event)
  7. Concurrent medical condition with a life expectancy of less than 12 months.
  8. Known severe renal failure (serum creatinine level >2.5 mg/dl).
  9. History of bleeding diathesis or coagulopathy or inability or unwillingness to receive blood transfusions.
  10. Evidence of active gastrointestinal bleeding or a history of such bleeding that is not known to have been treated and proven to have resolved.
  11. History of hepatitis (viral, ischemic or chemically-induced); clinical jaundice, history of cirrhosis.
  12. Patient treated with anticoagulant medication (Coumadin, LMWH)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00950339

Locations
Israel
Tel Aviv Medical Center
Tel Aviv, Israel
Sponsors and Collaborators
Tel-Aviv Sourasky Medical Center
Tel Aviv Medical Center
Investigators
Study Chair: Shmuel Banai, MD Tel Aviv Medical Center, Israel
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: michal roll, Interventional cardiologist, Tel-Aviv Sourasky Medical Center
ClinicalTrials.gov Identifier: NCT00950339     History of Changes
Other Study ID Numbers: TASMC-09-SB-0196-09-TLV-CTIL 
Study First Received: April 19, 2009
Last Updated: July 6, 2016
Health Authority: Israel: Ethics Commission
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Tel-Aviv Sourasky Medical Center:
GI bleeding
clopidogrel
aspirin
prevention
angiography

Additional relevant MeSH terms:
Heart Diseases
Hemorrhage
Coronary Disease
Coronary Artery Disease
Myocardial Ischemia
Gastrointestinal Hemorrhage
Cardiovascular Diseases
Pathologic Processes
Vascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Gastrointestinal Diseases
Digestive System Diseases
Polystyrene sulfonic acid
Clopidogrel
Famotidine
Omeprazole
Pantoprazole
Histamine H2 Antagonists
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Anti-Ulcer Agents

ClinicalTrials.gov processed this record on July 26, 2016